Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine kinase. It functions as a key regulator of numerous signaling pathways. It phosphorylates and inactivates glycogen synthase, a key enzyme in glycogen metabolism. It has also been shown to be involved in the regulation of a diverse array of cellular functions, including protein synthesis, cell proliferation, cell differentiation, microtubule assembly/disassembly, and apoptosis. Two isoforms of GSK-3 have been reported in mammals: an approximately 51 kDa GSK-3 alpha form and an approximately 47 kDa GSK-3 beta form. These two isoforms exhibit about 98% homology in their kinase domains. Other regions share less homology: they share only about 36% identity in the last 76 C-terminal amino acid residues.
Double-stranded RNA molecules (dsRNA) have been shown to block gene expression in a highly conserved regulatory mechanism known as RNA interference (RNAi). WO 99/32619 (Fire et al.) disclosed the use of a dsRNA of at least 25 nucleotides in length to inhibit the expression of genes in C. elegans. dsRNA has also been shown to degrade target RNA in other organisms, including plants (see, e.g., WO 99/53050, Waterhouse et al.; and WO 99/61631, Heifetz et al.), Drosophila (see, e.g., Yang, D., et al., Curr. Biol. (2000) 10:1191-1200), and mammals (see WO 00/44895, Limmer; and DE 101 00 586.5, Kreutzer et al.).